Rare Daily Staff

Bluebird Bio said that the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee has concluded that the benefit-risk balance of its Zynteglo gene therapy remains favorable and the company has lifted its voluntary marketing suspension.

“Patient safety remains our top priority,” said Andrew Obenshain, president of severe genetic diseases at Bluebird Bio. “To this end, we are grateful to the PRAC for its comprehensive review of the available evidence and positive recommendation for Zynteglo.”

No cases of hematologic malignancy have been reported in any patient who has received treatment with Zynteglo. However, because it is manufactured using the same BB305 lentiviral vector used in LentiGlobin for sickle cell disease, Bluebird Bio decided to temporarily suspend marketing of Zynteglo while the root cause of the safety events reported earlier this year for LentiGlobin for SCD were investigated by the company and assessed by the PRAC.

As previously announced on June 7, 2021, the U.S. Food and Drug Administration lifted the clinical holds on the phase 1/2 HGB-206 and phase 3 HGB-210 studies of LentiGlobin for SCD following the Agency’s review of the data.

As a next step, the recommendation will be forwarded to the Committee for Advanced Therapies and Committee for Medicinal Products for Human Use for adoption. The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all EU Member States.

Transfusion-Dependent Beta Thalassemia (TDT) is an inherited blood disorder that reduces the production of hemoglobin, leading to a lack of oxygen in many parts of the body and anemia, which lead to the need for chronic blood transfusions for survival and treatment for iron overload due to the transfusions.

Zynteglo is a one-time gene therapy that adds functional copies of a modified form of the beta-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once a patient has the βA-T87Q-globin gene, they have the potential to produce HbAT87Q, which is gene therapy-derived adult hemoglobin (Hb), at levels that may eliminate or significantly reduce the need for transfusions. In studies, transfusion independence is defined as no longer needing red blood cell transfusions for at least 12 months while maintaining a weighted average Hb of at least 9 g/dL.

The European Commission granted conditional marketing authorization (CMA) for Zynteglo gene therapy, for patients 12 years and older with TDT who do not have a beta0/beta0 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate, but a human leukocyte antigen (HLA)-matched related HSC donor is not available. Non-serious adverse events (AEs) observed during clinical studies that were attributed to Zynteglo included abdominal pain, thrombocytopenia, leukopenia, neutropenia, hot flush, dyspnea, pain in extremity, tachycardia and non-cardiac chest pain. One serious adverse event of thrombocytopenia was considered possibly related to Zynteglo.

The FDA granted Orphan Drug status and Breakthrough Therapy designation to Zynteglo for the treatment of TDT. Bluebird Bio is on track to complete its rolling Biologics License Application submission to the FDA for Zynteglo in mid-2021. This submission is anticipated to include adults, adolescents, and children with transfusion dependent beta-thalassemia across all genotypes (including non-β0/β0 genotypes and β0/β0 genotypes). Zynteglo is not approved in the United States.

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